rs56164683

Variant names:

• chr1-10306707-A-G
• rs56164683
• ENST00000377083.5:c.*2060A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000377083.5(KIF1B):​c.*2060A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 857,810 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (40 hom., cov: 25)
  • Exomes 𝑓: 0.025 (263 hom.)
• Consequence: KIF1B ENST00000377083.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 1 publications found

Genes affected

KIF1B (HGNC:16636): (kinesin family member 1B) Predicted to enable microtubule binding activity and plus-end-directed microtubule motor activity. Predicted to be involved in chemical synaptic transmission; dense core granule cytoskeletal transport; and vesicle-mediated transport. Predicted to act upstream of or within mitochondrion transport along microtubule. Predicted to be located in cytoplasmic vesicle membrane and neuron projection. Predicted to be part of kinesin complex. Predicted to be active in several cellular components, including axon; dendrite; and microtubule. Implicated in Charcot-Marie-Tooth disease type 2A1; carcinoma (multiple); multiple sclerosis; neuroblastoma; and pheochromocytoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

RN7SL731P (HGNC:46747): (RNA, 7SL, cytoplasmic 731, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0197 (2769/140902) while in subpopulation NFE AF = 0.0286 (1877/65718). AF 95% confidence interval is 0.0275. There are 40 homozygotes in GnomAd4. There are 1355 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2769 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377083.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	NM_001365951.3	MANE Select	c.2115+9461A>G		intron	N/A	NP_001352880.1
	KIF1B	NM_001365953.1		c.*2060A>G		3_prime_UTR	Exon 21 of 21	NP_001352882.1
	KIF1B	NM_183416.4		c.*2060A>G		3_prime_UTR	Exon 21 of 21	NP_904325.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF1B	ENST00000377083.5	TSL:1	c.*2060A>G		3_prime_UTR	Exon 21 of 21	ENSP00000366287.1
	KIF1B	ENST00000377093.9	TSL:1	c.*2060A>G		3_prime_UTR	Exon 21 of 21	ENSP00000366297.4
	KIF1B	ENST00000676179.1	MANE Select	c.2115+9461A>G		intron	N/A	ENSP00000502065.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2769 AN: 140802 Hom.: 40 Cov.: 25

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.0169

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00976

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000978

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0123

GnomAD4 exome AF: 0.0255 AC: 18252 AN: 716908 Hom.: 263 Cov.: 10 AF XY: 0.0256 AC XY: 8539 AN XY: 333626

African (AFR) AF: 0.00315 AC: 45 AN: 14308

American (AMR) AF: 0.0141 AC: 25 AN: 1772

Ashkenazi Jewish (ASJ) AF: 0.00629 AC: 41 AN: 6514

East Asian (EAS) AF: 0.000217 AC: 2 AN: 9218

South Asian (SAS) AF: 0.00174 AC: 24 AN: 13754

European-Finnish (FIN) AF: 0.0593 AC: 14 AN: 236

Middle Eastern (MID) AF: 0.00386 AC: 6 AN: 1554

European-Non Finnish (NFE) AF: 0.0273 AC: 17591 AN: 644460

Other (OTH) AF: 0.0201 AC: 504 AN: 25092

GnomAD4 genome AF: 0.0197 AC: 2769 AN: 140902 Hom.: 40 Cov.: 25 AF XY: 0.0199 AC XY: 1355 AN XY: 67964

African (AFR) AF: 0.00482 AC: 184 AN: 38174

American (AMR) AF: 0.0159 AC: 211 AN: 13294

Ashkenazi Jewish (ASJ) AF: 0.00976 AC: 33 AN: 3382

East Asian (EAS) AF: 0.00 AC: 0 AN: 4324

South Asian (SAS) AF: 0.000978 AC: 4 AN: 4088

European-Finnish (FIN) AF: 0.0479 AC: 421 AN: 8780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0286 AC: 1877 AN: 65718

Other (OTH) AF: 0.0122 AC: 24 AN: 1970

Alfa AF: 0.0208 Hom.: 7

Bravo AF: 0.0156

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56164683; hg19: chr1-10366765;